Content uploaded by Mauro Di Pasquale
Author content
All content in this area was uploaded by Mauro Di Pasquale on Apr 09, 2017
Content may be subject to copyright.
© 2008 Dr. Mauro Di Pasquale, MetabolicDiet.com Inc.
These statements have not been evaluated by the Food and Drug Administration.
The Essentials of Essential Fatty Acids
Introduction
Increasingly over the past few decades research is showing that supplementing your diet
with essential fatty acids (EFAs) can keep you out of harms way, help deal with certain
diseases, provide a foundation for optimal health, and improve body composition, and
mental and physical performance.1,2,3,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11
As well, some other fatty acids and companion compounds have also been shown to have
significant effects on health and body composition and can work additively or even
synergistically with the essential fatty acids.
Dietary Fats
Dietary fats are essential for normal
metabolism and good health. Not only
are they necessary for the proper
absorption, transportation and
function of the fat-soluble vitamins A,
D, E, and K, fats are used by the body
to produce cellular components,
hormones and other compounds that
are essential to the proper functioning
of the body. As well, a moderate
intake of fat is essential for
maximizing body composition and
decreasing body fat.
But while all fats, including saturated
fatty acids, have an important role in
energy metabolism and body
functions, the most important fats are
the essential fatty acids (EFAs) since
the body needs them to survive.
While the human body can manufacture most of the fats it needs from other fats,
carbohydrates and protein, including cholesterol, saturated fatty acids and unsaturated
fatty acids, there are two groups of fatty acids, called essential fatty acids, based on
linoleic acid (omega 6 group – which includes GLA) and alpha-linolenic acid (omega 3
group which includes EPA and DHA), which cannot be manufactured in the body.
The body cannot make an omega-3 or omega-6 fatty acid because human metabolism
cannot add a double-bond to a fatty acid that is more than 9 carbons away from the delta
end. For the same reason, the body cannot interconvert omega-3 and omega-6 fatty acids.
www.metabolicdiet.com Page 2 of 21
Unfortunately, for various reasons, many people are EFA challenged.
EFA Deficiency
Why are EFAs, especially the omega-3s, deficient in modern diets? Part of the problem is
the food that’s given to livestock and poultry. It’s a lot different from the natural food that
these animals would normally consume in the wild or even in the past.
So while both omega-3 (alpha-linolenic acid) and omega-6 (linoleic acid) are plentiful in the
leafy plants consumed by roaming animals, providing nearly equal ratios of these EFAs,
that’s no longer the case when they’re switched from grass to grains. The result is that the
fat in wild game and grazing ruminant contains roughly seven times more omega-3 fatty
acids than animals raised for commercial meat.
Another reason is that processing or cooking changes healthy EFAs into unhealthy trans-
fatty acids. So the meat and eggs that we consume today that’s already low in omega-3s is
even more depleted once it reaches our tables.
As well, we consume a lot of vegetable oils most of which are rich in omega-6 fatty acids
and poor in the omega-3s.
The increased omega-6/omega-3 ratio common to our modern diets, but not to man during
most of his existence, can give rise to disturbances in cellular structure and function, and
an increase in systemic inflammation, which can lead to dysfunction and disease.
So although you can get the EFAs you need from food, you have to know what you’re
doing and what you’re eating (and perhaps more importantly what you’re eating was
eating), and even then, although you’re trying to eat right, you likely will still need to
supplement your diet with some of the essential fatty acids.
The Secrets of EFAs: How the Omegas Work
Alpha linolenic acid is the principal essential fatty acid in the omega-3 family and linoleic
acid takes the lead in the omega-6 series. In a healthy body with sound nutrition, various
metabolic conversions take place transferring the raw dietary materials into usable,
biologically potent EFAs and other compounds.
Alpha linolenic acid is transformed into eicosapentaenoic acid (EPA) and later into
docosahexaenoic acid (DHA). The series three prostaglandins are formed from EPA. As
well, EPA reduces the production of the bad prostaglandins from arachidonic acid.
The omega-6 linoleic acid converts to gamma linolenic acid (GLA). Both the EPA and the
GLA synthesized from dietary sources undergo another conversion, resulting in hormone-
like biochemical compounds know as eicosanoids. These substances aid in virtually every
www.metabolicdiet.com Page 3 of 21
body activity, from vital organ functioning down to intracellular processes, including helping
to regulate inflammation and blood pressure as well as heart, gastrointestinal, and kidney
functions.
As such, their use can be preventative and therapeutic for various conditions including
some types of cancer, and cardiovascular, neurological and musculoskeletal diseases.
Because of their anti-inflammatory properties they are effective anti-aging nutrients. As
well, they can be used as an aid for weight loss and for improving body composition.
Omega 3 Fatty Acids
Omega-3 fatty acids are long chain polyunsaturated fatty acids that have biological
functions because they are converted to a number of active substances in the body such
as prostaglandins and leukotrienes and are involved in a number of metabolic events.
Linolenic acid is an essential fatty acid since it cannot be synthesized in the body. Other
omega-3 fatty acids can, however, be synthesized from linolenic acid.
Omega 3 and omega 6 fatty acids are precursors for hormones and determine the
composition of our cell membranes, influencing the production of pro- and anti-
inflammatory substances.12
Omega-3 fatty acids, found in fish oils (mainly EPA and DHA) and flaxseed oil, are useful
in a wide variety of conditions:13 They have been shown to:
1. Reduce oxidant stress14 (oxidative stress or free radical damage is a factor of
importance in the development of inflammatory events).
2. Suppress the production of pro-inflammatory compounds in the body and
therefore influence inflammatory conditions such as arthritis, diabetes,
inflammatory bowel disease, cancer, autoimmune disorders, and
aging.15,16,17,18,19,20,21,22,23, 24,25,26,27 28,29,30
3. Improve serum lipids and provide cardiovascular protection,31,32,33,34,35
4. Provide protection against stress,36 cognitive aging37,38 and depression.39
5. Blood pressure, clotting, immune response, insulin resistance, and
triglyceride levels are all positively affected by the omega-3s in EFA+.40
6. May be effective in the prevention of coronary heart disease,41,42 and
headaches.43
7. Aid in weight and fat loss, especially when combined with CLA (see below).
8. Be positively associated with peak bone density in young men.44
While it’s generally known that EFAs are good for the cardiovascular system and for
arthritis, it’s not as well known the EFAs can affect mental health. In fact, a deficiency in
EFAs or too little omega 3 fatty acids can lead to decreased mental health, depression and
even aggressive tendencies.
EFAs have been shown to assist in treating depression and other mental health conditions.
Low levels of omega-3 EFAs are common in depression. In one 2002 study, researchers
www.metabolicdiet.com Page 4 of 21
found that treatment with EPA improved outcomes in patients with persistent depression.45
Another study found that EPA may prove an effective add-on treatment in schizophrenia.46
There is even some evidence that the decrease in omega 3 consumption may be
responsible for increasing homicide rates.47
Part of omega-3's effectiveness in treating brain disorders and the reason why lack of
omega 3’s results in some mental aberrations may be linked to its role in
neurotransmission and brain development. DHA in particular is crucial for proper brain
function, and pregnant women are advised to consume adequate levels for fetal brain
development.
A recent paper published in 2005 concluded:48
There is no doubt that cerebral lipids, and EFA-derived LC-PUFAs in particular, have
significant direct and indirect actions on cerebral function. Not only does the lipid
composition of neural membranes affect the function of their embedded proteins, but also
many LC-PUFAs are converted to neurally active substances.
There is good evidence that psychiatric illness is associated with depletion of EFAs and,
crucially, that supplementation can result in clinical amelioration. As well as challenging
traditional views of aetiology and therapeutics in psychiatry, the clinical trial data may
herald a simple, safe and effective adjunct to our standard treatments for many disabling
conditions.
EFAs and Body Composition and Exercise Performance
Besides all the health benefits above, the EFAs may also be useful in improving body
composition and exercise performance, They have been shown to affect insulin sensitivity
and growth hormone secretion, have anti-catabolic effects, both enhance weight loss and
help keep the weight off, and influence exercise performance.
Fish oil may, through perhaps more than one mechanism, have anti-catabolic properties.
By extrapolating from burn injury studies, there is the possibility of modifying the catabolic
processes secondary to training through the use of fish oil.49,50 There is the possibility that
fish oil may modulate PGE sub 2-mediated muscle proteolysis.
Studies have shown that the mechanism of interleukin-1 (IL-1)-induced muscle proteolysis
involves PGE sub 2 synthesis.51 Thus it is likely that omega-3 fatty acids from fish oil
competitively inhibit the PGE sub 2 synthesis,52,53 resulting in less muscle proteolysis.
Furthermore, it has been shown that fish oil feeding in healthy volunteers can reduce the in
vitro production of IL-1 and tumor necrosis factor by macrophages.54 Thus, the reduction of
IL-1 level may represent another mechanism by which fish oil moderates muscle
proteolysis.
www.metabolicdiet.com Page 5 of 21
Omega-3 fatty acids may increase growth hormone secretion since they are involved in the
formation of prostaglandin E1, which in turn is involved in GH release.55 As well, to add to
the possible benefits in improving exercise performance and body composition,
Several studies have shown that fish oil increases insulin sensitivity, the breakdown of
body fat and the use of fat as a primary energy source. As such, besides decreasing
inflammation and increasing cardiovascular health, they also provide substantial weight
and fat loss benefits.
LNA, EPA, and DHA can enhance lipolysis (body fat breakdown)56,57 and decrease
lipogenesis (body fat formation).58,59 The combined breakdown of stored body fat and
decrease in additional body fat can have very positive results for the dieter. You actually
end up making less and breaking down more body fat when using these oils.
As well, a recent study found that GLA reduced weight regain in humans following major
weight loss, suggesting a role for essential fatty acids in fuel partitioning in humans prone
to obesity.60
A recent study61 in horses found that n-3 fatty acids laced vitamin supplement induced
changes in membrane composition, which modulated the decrease in erythrocyte
membrane fluidity seen during exercise, and therefore found to be potentially beneficial in
exercising horses.
Gamma linolenic acid
Gamma linolenic acid (GLA) is important for health and has suppressive effects on both
acute and chronic inflammation, and effects on decreasing the response to anxiety and
stress.62,63,64,65,66,67,68 It also works synergistically with some of the essential fatty acids to
decrease inflammation and stress responses.69,70,71
GLA is needed by the body for the manufacture of certain hormone-like substances called
Prostaglandins. These substances have beneficial regulatory effects on the immune
system, circulation and the menstrual cycle. Their purpose is to help control and regulate
cell growth and to maintain hormonal balance. Also helps to maintain healthy skin.
The use of EPA with GLA (as in EFA+) decreases some of the possible inflammatory
effects of using GLA supplements. That’s because GLA can be a precursor for arachidonic
acid (AA, a “bad” type of prostaglandin that increases platelet aggregation and
inflammation) and the addition of EPA reduces AA accumulation in some cells and tissues
secondary to GLA supplementation.72
A recent study found that GLA reduced weight regain in humans following major weight
loss, suggesting a role for essential fatty acids in fuel partitioning in humans prone to
obesity.73
www.metabolicdiet.com Page 6 of 21
Conjugated Linoleic Acid (CLA)
Conjugated Linoleic Acid (CLA), while
not an essential fatty acid, has
significant effects on body composition.
It’s a mixture of isomers of linoleic acid,
which is found preferentially in dairy
products, meat, and in cheese, milks
and yogurt that have undergone heat
treatment.
CLA has been shown to have properties
above and beyond those of linoleic acid.
It has shown potential as a powerful
anticarcinogen74,75 and exhibits potent
antioxidant activity.76 Studies have suggested that CLA may be cytotoxic to human cancer
cells in vivo.77
CLA has a wide range of biological effects.78 It has potent antioxidant activity and has
shown potential as an anticarcinogen. CLA has been shown to have significant anti-
inflammatory properties79 and to inhibit inflammatory mediators such as PGE2, IL-6, and
TNF-alpha,80,81 and also acts as a COX-2 inhibitor.82,83
Studies in animals and humans indicate that CLA supplementation decreases body fat and
increases lean muscle mass. The increase in lean muscle mass is most pronounced in
individuals who are exercising regularly.
CLA appears to reduce the ability of fat cells to take up fats from the bloodstream; it also
inhibits the formation of new fat cells. CLA also helps cells burn fat at a higher rate, while
fueling and preserving muscle, leading to a reduction in fat and an increase in lean muscle
mass.
Numerous physiological effects in relation to body-weight control have been attributed to
CLA in animals. In different animal models, CLA has been shown to reduce body fat and to
increase lean body mass.84,85 But CLA has marked effects in humans as well and has
been found to decrease body fat mass and support muscle mass in overweight humans.
86,87,88,89
For example, a study published in the International Journal of Obesity found that those
who were given CLA for a four week period had significant decreases in abdominal fat.90
As well, a recent study concluded that long term CLA supplementation not only helps to
decrease body fat but also helps to maintain weight loss in the long term. A recent long
term study found that a mixture of the two CLA isomers significantly lowered body fat mass
in overweight humans at both 1 and 2 years.9192 It likely does this by affecting various
enzymes involved in lipid formation and to a lesser extent enhancing fat breakdown.93, 94, 95
www.metabolicdiet.com Page 7 of 21
As well, CLA seems to have significant effects on weight regain, as it reduces fat uptake
into adipocytes by decreasing the formation of fat and but not affecting fat breakdown. It
likely does this by affecting various enzymes involved in lipid formation rather than
enhancing fat breakdown, known as lipolysis.96,97,98
Thus there is an overall increase in fat breakdown since the two processes are usually in
dynamic equilibrium with as much fat being produced as is broken down. Decreasing fat
formation changes the dynamics to one of overall increased fat breakdown and
subsequently a decrease in overall body fat.
Of equal importance, for those wishing to maximize lean body mass, is the possible anti-
catabolic effects of CLA.99,100
The most recent study in a series of studies of the effects of CLA confirmed and expanded
on the findings of the previous studies: CLA reduces body fat mass in specific regions of
the body, especially the abdominal area in both men and women, and maintains or
increases lean body mass.101
Adding to CLA’s effects on body composition, another recent study found that CLA
supplementation even increased fat oxidation and energy expenditure during sleep.102
Conclusion
The bottom line is that the essential fatty acids, and some non essential fatty acids such as
CLA, have significant effects on body composition, training, recovery, and can also
increase overall health and well being.
www.metabolicdiet.com Page 8 of 21
EFA+
EFA+
Version
Version
Version
III
III
Essential Fatty Acids – Plus
EFA+ is an enhanced ess ential fatty acid
formula containing optimum levels of the
essential fatty acids as well as several
other additive and synergistic ingredients.
The complex, scientifically based
formulation provides much more than
other essential fatty acid products.
Be side s the es sential fatty acids, EFA+
also contains numerous other ingredients
that provide other benefits including
weight and fat los s, and improvements in
body composition.
WWW
WWW
.
.
MD
MD
EFA
EFA
PLUS
PLUS
.
.
COM
COM
EFA+ An Essential Fatty Acid Formulat
EFA+ An Essential Fatty Acid Formulat
i
i
on
on
, and
, and
, and
More
More
www.metabolicdiet.com Page 9 of 21
Ingredients in EFA+
I formulated EFA+ to be a balanced combination of essential fatty acids (EFAs), and other
ingredients that work additively and synergistically to maximize the beneficial effects of the
essential fatty acids on health, inflammation and body composition.
As far as the essential fatty acids, EFA+ consists largely of the omega 3 family of essential
fatty acids, so as to even out the omega 6/omega 3 ratio to one that is closer to the ratio
that man has consumed for most of his existence. Bringing the ratio into line enhances
cellular function, decreases inflammation, and improves body composition, health and
well-being.
EFA+ contains pharmaceutical grade fish oil with higher levels of EPA and DHA. It’s
important to include these longer carbon chain omega 3s for two reasons. First of all as
first of all the formation of EPA and DHA from ALA is limited and secondly while fish is one
method of getting these oils, most sources recommend that fish consumption be limited to
two to three servings weekly because so many fish are tainted with mercury, PCBs and
other contaminants.
High-quality, purified fish oil, as found in EFA+ are contaminant free and present a viable
alternative to frequent consumption of fish.
But there are many more active ingredients in EFA+ that enhance its effects. For example,
the co-factors zinc, magnesium, Vitamins. C, B3 and B6 must be present for the benefits of
the essential fatty acids to be realized.
Some of the added vitamins and minerals, besides optimizing the use of the essential fatty
acids, also have other beneficial properties related to the effects of the essential fatty
acids. For example vitamins B3 and B6 have significant antioxidant properties and also
beneficial effects on serum cholesterol and triglycerides. Magnesium and zinc are also
heart friendly and have beneficial effects on the immune, cardiovascular and
neuromuscular systems.
EFA+ also contains several lipotropic factors and other ingredients, including conjugated
linoleic acid, L-carnitine, methionine, serine, choline and inositol that optimize the
utilization, transport and metabolism of fat, working to decrease body fat, normalize serum
lipids including cholesterol, enhance energy levels, and fight inflammation in the body.
The antioxidants present in EFA+ serve several purposes. First of all they help preserve
the natural state of the EFAs by protecting them from oxidative damage and becoming
rancid while in the capsule so that what you get are all the good effects that EFA+ has to
offer and none of the bad.
That’s one of the reasons why EFA+ combines several antioxidants, including vitamin A,
vitamin C, vitamin E, conjugated linoleic acid (CLA), alpha lipoic acid, and
glutathione, with fish oil and other sources of essential fatty acids.103, 104
www.metabolicdiet.com Page 10 of 21
As well, the association of antioxidants with the omega-3 essential fatty acids, such as the
fish oil and other ingredients found in EFA+, act in concert to enhance the beneficial
effects of the essential fatty acids on inflammation and on the immune and cardiovascular
systems.105,106
On top of all this the antioxidants counteract some of the adverse effects that these
essential fatty acids might have. For example, although it’s been shown that fish oil
increases oxidation of LDL cholesterol, the “bad” cholesterol in the body that’s been
implicated in cardiovascular disease, it has also been shown that the use of antioxidants
counteracts this negative effect of fish oil.107,108
Omega-3, 6 and 9 Oils
EFA+ contains omega 3, 6 and 9 fatty acids, including EPA and DHA, the longer chain
fatty acids found mostly in fish oil. The plant based oils are mechanically pressed under
low heat, light and oxygen-free environment ensuring the extremely high quality of the
formula. As well, pharmaceutical grade fish oil is used in the formulation. The formula is
mercury free and free of harmful trans fatty acids.
The emphasis in EFA+ is on the omega 3 essential fatty acids and on GLA, an important
omega 6 fatty acid, but EFA+ also contains omega 6 linoleic acid as part of flax seed oil
and oleic acid, an omega-9 fatty acid, which is also present as a natural constituent of flax
seed oil.
Conjugated Linoleic Acid and Gamma linolenic acid (GLA)
Both CLA and GLA have health and body composition effects and are included in EFA+.
The use of EPA with GLA (as in EFA+) decreases some of the possible inflammatory
effects of using GLA supplements. That’s because GLA can be a precursor for arachidonic
acid (AA, a “bad” type of prostaglandin that increases platelet aggregation and
inflammation) and the addition of EPA reduces AA accumulation in some cells and tissues
secondary to GLA supplementation.109
Choline, Phosphatidylcholine, Phosphatidylserine, Serine and
Policosanol
Choline, phosphatidylcholine, phosphatidylserine, and serine are involved in phospholipid
metabolism and augment the effects of the EFAs on cell wall structure and integrity, as
well as molecular signaling properties.110 These ingredients are needed for cell membrane
integrity and to facilitate the movement of signaling compounds between cells and the
movement of fats in and out of cells.111 They have significant effects on nerve cell
membranes, and are required for nerve growth and function.112
www.metabolicdiet.com Page 11 of 21
Policosanols are a blend of compounds isolated from natural plant waxes. Policosanol
contains several long chain fatty alcohols, including octacosanol, hexacosanol and
triacontanol. Animal and in-vitro research has shown that these compounds may support
the cardiovascular system and inhibit lipid peroxidation as well as support macrophage
activity.
Policosanol helps lower cholesterol levels by slowing the body's own production of
cholesterol in the liver, as well as reducing the risk of blood clots and enhancing
circulation. Some studies have shown that policosanol, like some EFAs can significantly
reduce both total cholesterol and LDL (bad) cholesterol.113,114,115,116
As well, policosanol, due mainly to the abundant octacosanol, has several other beneficial
effects including increasing muscle endurance, increasing the efficiency of blood flow, and
helping to stabilize cell membranes.117,118,119 Octacosanol may also be useful for
improving athletic performance as suggested by some studies.120,121
Alpha Lipoic Acid
Alpha lipoic acid (ALA) has potent antioxidant properties intrinsically and secondary to its
ability to increase levels of intra-cellular glutathione, and its ability to recycle other
antioxidants such as vitamin C, vitamin E and glutathione.122,123,124,125,126 ALA and
glutathione have been shown to have significant effects in decreasing mercury toxicity in
the body.127
Alpha lipoic acid also has significant anti-inflammatory properties and has been shown to
inhibit IL-1, a proinflammatory cytokine and also inhibit the synthesis of PGE2 by inhibiting
COX-2 activity.
ALA’s ability to decrease both the pro-inflammatory cytokines128129 and secondary cortisol
elevations, along with similar effects from CLA, simulates the anti-inflammatory effects of
the present class of NSAIDS such as Celebrex, Advil, Aleve, etc. As well, EFA+ contains
fish oil with substantial amounts of DHA and EPA, which has also been shown to have
effects similar to the anti-inflammatory prescription and OTC drugs.130
ALA has been shown to inhibit cross-linking among proteins, a process that contributes to
the aging process in the body and especially in collagen-heavy tissues such as skin.
Alpha-lipoic acid activates a collagen-regulating factor known as AP-1 that turns on
enzymes that digest glycation-damaged collagen and thus make the skin more supple and
youthful looking.
Besides having potent antioxidant and anti-inflammatory effects, ALA also has significant
anabolic effects secondary to its beneficial effects on insulin sensitivity and growth
hormone and IGF-I secretion, all factors involved in maintaining, repairing and
regenerating musculoskeletal tissues.131,132,133,134
www.metabolicdiet.com Page 12 of 21
ALA is also useful in reversing mitochondrial dysfunction, especially in aging
mitochondria.135,136
The many benefits of EFA+ include:
• Effects on body composition – improved metabolism, enhanced weight and fat loss
and retention of muscle mass.
• Increased insulin sensitivity.
• Decreased inflammation in the body thus providing cardiovascular, neural,
musculoskeletal, and hormonal (including testosterone and growth hormone) health
benefits.
• Improved serum lipid (cholesterol, triglycerides) profile including cholesterol levels.
• Improved immune system functioning.
• Improved mental health.
• Anti-aging effects.
Bottom Line
The bottom line is that EFA+ is a multi-purpose formulation designed to provide the full
gamut of all the essential fatty acids and supporting ingredients that are so important in
optimizing your metabolism, enhancing weight loss, body composition, and the anabolic
and fat burning effects of exercise, boosting your immune system and decreasing counter
productive inflammation in the body secondary to exercise, aging and various diseases.
www.metabolicdiet.com Page 13 of 21
EFA+ Nutritional Panel
www.metabolicdiet.com Page 14 of 21
References:
1 Carrero JJ, Fonolla J, Marti JL, Jimenez J, Boza JJ, Lopez-Huertas E. Intake of fish oil,
oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive
protein and reduces coronary heart disease risk factors in male patients in a cardiac
rehabilitation program. J Nutr. 2007 Feb;137(2):384-90.
2 Hosli I, Zanetti-Daellenbach R, Holzgreve W, Lapaire O. Role of omega 3-fatty acids and
multivitamins in gestation. J Perinat Med. 2007;35 Suppl 1:S19-24.
3 Gaullier JM, Halse J, Hoivik HO, Hoye K, Syvertsen C, Nurminiemi M, Hassfeld C,
Einerhand A, O'Shea M, Gudmundsen O. Six months supplementation with conjugated
linoleic acid induces regional-specific fat mass decreases in overweight and obese. Br J
Nutr. 2007 Mar;97(3):550-60.
4 Mosley BS, Hobbs CA, Flowers BS, Smith V, Robbins JM. Folic acid and the decline in
neural tube defects in Arkansas. J Ark Med Soc. 2007 Apr;103(10):247-50.
5 Gariballa S, Forster S. Effects of dietary supplements on depressive symptoms in older
patients: A randomised double-blind placebo-controlled trial. Clin Nutr. 2007 Jul 25;
[Epub ahead of print]
6 Hu J, Morrison H, Mery L, DesMeules M, Macleod M; Canadian Cancer Registries
Epidemiology Research Group. Diet and vitamin or mineral supplementation and risk of
colon cancer by subsite in Canada. Eur J Cancer Prev. 2007 Aug;16(4):275-91
7 [No authors listed] Folic acid. Good for brain health. Mayo Clin Health Lett. 2007
Jul;25(7):6.
8 Nykamp D, Kavanaugh ED, Wenker AP. Vitamins: the wise choice for women with
cardiovascular disease. Consult Pharm. 2007 Jun;22(6):490-502.
9 Tipoe GL, Leung TM, Hung MW, Fung ML. Green tea polyphenols as an anti-oxidant and
anti-inflammatory agent for cardiovascular protection. Cardiovasc Hematol Disord Drug
Targets. 2007 Jun;7(2):135-44.
10 Houston MC. Treatment of hypertension with nutraceuticals, vitamins, antioxidants and
minerals. Expert Rev Cardiovasc Ther. 2007 Jul;5(4):681-91
11 Machefer G, Groussard C, Vincent S, Zouhal H, Faure H, Cillard J, Radak Z, Gratas-
Delamarche A. Multivitamin-mineral supplementation prevents lipid peroxidation during
"the Marathon des Sables". J Am Coll Nutr. 2007 Apr;26(2):111-20.
12 Song C, Li X, Leonard BE, Horrobin DF. Effects of dietary n-3 or n-6 fatty acids on
interleukin-1beta-induced anxiety, stress, and inflammatory responses in rats. J Lipid
Res. 2003;44(10):1984-91.
13 Schmidt GR. Therapeutics Of Fish Oil. Abstract of Meeting Presentation. ASHP Annual
Meeting 1989;46:1-33.
14 Mori TA, Puddey IB, Burke V, Croft KD, Dunstan DW, Rivera JH, Beilin LJ. Effect of
omega 3 fatty acids on oxidative stress in humans: GC-MS measurement of urinary F2-
isoprostane excretion. Redox Rep 2000;5(1):45-6.
15 Siddiqui RA, Shaikh SR, Sech LA, Yount HR, Stillwell W, Zaloga GP. Omega 3-fatty
acids: health benefits and cellular mechanisms of action. Mini Rev Med Chem.
2004;4(8):859-71.
16 Trebble TM, Wootton SA, Miles EA, et al. Prostaglandin E2 production and T cell
function after fish-oil supplementation: response to antioxidant cosupplementation. Am J
Clin Nutr 2003;78: 376–82.
www.metabolicdiet.com Page 15 of 21
17 Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep.
2004;6(6):461-7.
18 Endres S, Ghorbani R, Kelly VE, et al. The effect of dietary supplementation with n-3
fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear
cells. N Engl J Med 1989;320: 265–70.
19 Adam O, Beringer C, Kless T, et al. Anti-inflammatory effects of a low arachidonic acid
diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 2003;23: 27–36.
20 Belluzzi A, Boschi S, Brignola C, Munarini A, Cariani G, Miglio F. Polyunsaturated fatty
acids and inflammatory bowel disease. Am J Clin Nutr 2000;71S: 339S–42S.
21 Hardman WE. (n-3) fatty acids and cancer therapy. J Nutr. 2004;134(12 Suppl):3427S-
3430S.
22 Nettleton JA, Katz R. n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a
review. J Am Diet Assoc. 2005;105(3):428-40.
23 Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am
Coll Nutr. 2002;21(6):495-505.
24 Kremer JM, Lawrence DA, Petrillo GF, et al. Effects of high-dose fish oil on rheumatoid
arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune
correlates. Arthritis Rheumatism 1995;38:1107-1114.
25 Esperson GT, Grunnet N, Lervang HH, et al. Decreased interleukin-1 beta levels in
plasma from rheumatoid arthritis patients after dietary supplementation with n-3
polyunsaturated fatty acids. Clin Rheumatol 1992;11:393-395.
26 Watkins BA, Li Y, Lippman HE, Seifert MF. Omega-3 polyunsaturated fatty acids and
skeletal health. Exp Biol Med (Maywood) 2001;226(6):485-97.
27 Tidow-Kebritchi S, Mobarhan S. Effects of diets containing fish oil and vitamin E on
rheumatoid arthritis. Nutr Rev 2001;59(10):335-8.
28 Kremer JM, Bigauoette J, Michalek AV, et al. Effects of manipulation of dietary fatty
acids on clinical manifestations of rheumatoid arthritis. Lancet 1985;1:184-187.
29 Herold PM, Kinsella JE. Fish oil consumption and decreased risk of cardiovascular
disease: a comparison of findings from animal and human feeding trials. Am J Clin Nutr
1986;43:566-598.
30 Kelley VE, Ferretti A, Izui S, Strom TB. A fish oil diet rich in eicosapentaenoic acid
reduces cyclo oxygenase metabolites and supresses lupus in MRL-lpr mice. J Immunol
1985;134:1914-1919.
31 Ismail HM. The role of omega-3 fatty acids in cardiac protection: an overview. Front
Biosci. 2005;10:1079-88.
32 Hjerkinn EM, Seljeflot I, Ellingsen I, Berstad P, Hjermann I, Sandvik L, Arnesen H.
Influence of long-term intervention with dietary counseling, long-chain n-3 fatty acid
supplements, or both on circulating markers of endothelial activation in men with long-
standing hyperlipidemia. Am J Clin Nutr. 2005;81(3):583-9.
33 Phillipson BE, Rothrock DW, Connor WE, Harris WS, Illingworth DR. Reduction of
plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with
hypertriglyceridemia. N Engl J Med 1985;312: 1210–6.
34 Shahidi F, Miraliakbari H. Omega-3 (n-3) fatty acids in health and disease: Part 1--
cardiovascular disease and cancer. J Med Food. 2004 Winter;7(4):387-401.
35 Jacobson TA. Beyond lipids: the role of omega-3 Fatty acids from fish oil in the
prevention of coronary heart disease. Curr Atheroscler Rep. 2007 Aug;9(2):145-53.
www.metabolicdiet.com Page 16 of 21
36 Bourre JM. Dietary Omega-3 Fatty Acids and Psychiatry: Mood, Behaviour, Stress,
Depression, Dementia and Aging. J Nutr Health Aging. 2005;9(1):31-38.
37 Whalley LJ, Fox HC, Wahle KW, Starr JM, Deary IJ. Cognitive aging, childhood
intelligence, and the use of food supplements: possible involvement of n-3 fatty acids. Am
J Clin Nutr. 2004;80(6):1650-7.
38 Maclean CH, Issa AM, Newberry SJ, Mojica WA, Morton SC, Garland RH, Hilton LG,
Traina SB, Shekelle PG. Effects of omega-3 fatty acids on cognitive function with aging,
dementia, and neurological diseases. Evid Rep Technol Assess (Summ). 2005;(114):1-3.
39 Su KP, Huang SY, Chiu CC, Shen WW. Omega-3 fatty acids in major depressive
disorder. A preliminary double-blind placebo-controlled trial. Eur Neuropsychopharmacol
2003;13:267–71.
40 Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr
1999;70(3):560S-569S.
41 Hodgson JM, Wahlqvist ML, Boxall JA, Balazs ND. Can linoleic acid contribute to
coronary artery disease?. American Journal of Clinical Nutrition 1993;58(2):228-234.
42 Cundiff DK, Lanou AJ, Nigg CR. Relation of omega-3 Fatty Acid intake to other dietary
factors known to reduce coronary heart disease risk. Am J Cardiol. 2007;99(9):1230-3.
43 Smith RS. The cytokine theory of headache. Med Hypotheses 1992;39(2):168-174.
44 Hogstrom M, Nordstrom P, Nordstrom A. n-3 Fatty acids are positively associated with
peak bone mineral density and bone accrual in healthy men: the NO2 Study. Am J Clin
Nutr. 2007;85(3):803-7.
45 Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in
patients with ongoing depression despite apparently adequate treatment with standard
drugs. Arch Gen Psychiatry. 2002;59(10):913-9.
46 Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ. Randomized, placebo-
controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in
schizophrenia. Am J Psychiatry. 2002;159(9):1596-8.
47 Hibbeln JR, Nieminen LR, Lands WE. Increasing homicide rates and linoleic acid
consumption among five Western countries, 1961-2000. Lipids. 2004;39(12):1207-13.
48 Hallahan B, Garland MR. Essential fatty acids and mental health. Br J Psychiatry.
2005;186:275-7.
49 Alexander JW, Saito H, Trocki O, Ogle CK. The importance of lipid type in the diet after
burn injury. Ann Surg 1986;204:1-8.
50 Trocki O, Heyd TJ, Waymack JP, Alexander JW. Effects of fish oil on postburn
metabolism and immunity. J Parent Enter Nutr 1987;11:521-528.
51 Baracos V, Rodemann HP, Dinarello CA, Goldberg AL. Stimulation of muscle protein
degradation and prostaglandin E sub 2 release by leukocytic pyrogen (interleukin-1). A
mechanism for the increased degradation of muscle proteins during fever. N Engl J Med
1983;308:553-558.
52 Goodnight SH, Harris WS, Connor WE, Illingworth DR. Polyunsaturated fatty acids,
hyperlipidemia and thrombosis. Arteriosclerosis 1982;2:87-111.
53 Needleman P, Raz M, Minkes MS, et al. Triene prostaglandins: prostaglandin and
thromboxane biosynthesis and unique biologic properties. Proc Natl Acad Sci
1979;76:944-948.
54 Endres S, Ghorbani R, Kelley VE, et al. The effect of dietary supplementation with n-3
polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by
mononuclear cells. N Engl J Med 1989;320:265-71.
www.metabolicdiet.com Page 17 of 21
55 Dray F, Kouznetzova B, Harris D, Brazeau P. Role of prostaglandins on growth hormone
secretion: PGE2 a physiological stimulator. Advances in Prostaglandin & Thromboxane
Research 1980;8:1321-8.
56 Awad AB, Zepp EA. Alteration of rat adipose tissue lipolytic response to norepinephrine
by dietary fatty acid manipulation. Biochem Biophys Res Comm 1979;86:138-144.
57 Parrish CC, Pathy DA, Parkes JG, Angel A. Dietary fish oils modify adipocyte structure
and function. J Cell Phys 1991;148(3):493-502.
58 Belzung F, Raclot T, Groscolas R. Fish oil n-3 fatty acids selectively limit the
hypertrophy of abdominal fat depots in growing fats fed high-fat diets. Am J Physiol
1993;264(6 Pt 2): R1111-R1118.
59 Parrish CC, Pathy DA, Angel A. Dietary fish oils limit adipose tissue hypertrophy in rats.
Metabolism: Clin Exp 1990;39(3):217-19.
60 Schirmer MA, Phinney SD. {gamma}-Linolenate Reduces Weight Regain in Formerly
Obese Humans. J Nutr. 2007;137(6):1430-5.
61 Portier K, de Moffarts B, Fellman N, Kirschvink N, Motta C, Letellierw C, Ruelland A, van
Erck E, Lekeux P, Couder J. The effects of dietary N-3 and antioxidant supplementation
on erythrocyte membrane fatty acid composition and fluidity in exercising horses. Equine
Vet J Suppl. 2006;(36):279-84.
62 Fan YY, Chapkin RS. Importance of dietary gamma-linolenic acid in human health and
nutrition. Journal of Nutrition 1998;128: 141114.
63 Furse RK, Rossetti RG, Seiler CM, Zurier RB. Oral administration of gammalinolenic
acid, an unsaturated fatty acid with anti-inflammatory properties, modulates interleukin-
1beta production by human monocytes. J Clin Immunol. 2002;22(2):83-91.
64 Tate G, Mandell BF, Laposata M, Ohliger D, Baker DG, Schumacher HR, Zurier RB.
Suppression of acute and chronic inflammation by dietary gamma linolenic acid. J
Rheumatol. 1989;16(6):729-34.
65 Johnson MM, Swan DD, Surette ME et al. Dietary supplementation with gamma-
linolenic acid alters fatty acid content and eicosanoid production in healthy humans.
Journal of Nutrition 1997;127: 143544.
66 Song C, Li X, Leonard BE, Horrobin DF. Effects of dietary n-3 or n-6 fatty acids on
interleukin-1beta-induced anxiety, stress, and inflammatory responses in rats. J Lipid
Res. 2003;44(10):1984-91.
67 DeLuca P, Rossetti RG, Alavian C, Karim P, Zurier RB. Effects of gammalinolenic acid
on interleukin-1 beta and tumor necrosis factor-alpha secretion by stimulated human
peripheral blood monocytes: studies in vitro and in vivo. J Investig Med. 1999;47(5):246-
50.
68 Kapoor R, Huang YS. Gamma linolenic acid: an antiinflammatory omega-6 fatty acid.
Curr Pharm Biotechnol. 2006 Dec;7(6):531-4.
69 Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH. Addition of
eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum
arachidonic acid accumulation in humans. J Nutr. 2000;130(8):1925-31.
70 Gillis RC, Daley BJ, Enderson BL, Karlstad MD. Eicosapentaenoic acid and gamma-
linolenic acid induce apoptosis in HL-60 cells. J Surg Res. 2002;107(1):145-53.
71 Gueck T, Seidel A, Baumann D, Meister A, Fuhrmann H. Alterations of mast cell
mediator production and release by gamma-linolenic and docosahexaenoic acid. Vet
Dermatol. 2004;15(5):309-14.
www.metabolicdiet.com Page 18 of 21
72 Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH. Addition of
eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum
arachidonic acid accumulation in humans. J Nutr 2000;130(8):1925-31.
73 Schirmer MA, Phinney SD. {gamma}-Linolenate Reduces Weight Regain in Formerly
Obese Humans. J Nutr. 2007;137(6):1430-5.
74 Ip C, Singh M, Thompson HJ, Scimeca JA. Conjugated linoleic acid suppresses
mammary carcinogenesis and proliferative activity of the mammary gland in the rat.
Cancer Research 1994;54(5):1212-5.
75 Ip C, Scimeca JA, Thompson HJ. Conjugated linoleic acid. A powerful anticarcinogen
from animal fat sources. [Review] Cancer 1994;74(3 Suppl):1050-4.
76 Pariza MW, Ha YL, Benjamin H, et al. Formation and action of anticarcinogenic fatty
acids. Advances in Experimental Medicine & Biology 1991;289:269-72.
77 Shultz TD, Chew BP, Seaman WR, Luedecke LO. Inhibitory effect of conjugated dienoic
derivatives of linoleic acid and beta-carotene on the in vitro growth of human cancer cells.
Cancer Letters 1992;63(2):125-33.
78 Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G. Biological effects of
conjugated linoleic acids in health and disease. J Nutr Biochem. 2006;17(12):789-810.
79 Zulet MA, Marti A, Parra MD, Martinez JA. Inflammation and conjugated linoleic acid:
mechanisms of action and implications for human health. J Physiol Biochem.
2005;61(3):483-94.
80 Luongo D, Bergamo P, Rossi M. Effects of conjugated linoleic acid on growth and
cytokine expression in Jurkat T cells. Immunol Lett 2003;90:195– 201.
81 Eder K, Schleser S, Becker K, Korting R. Conjugated linoleic acids lower the release of
eicosanoids and nitric oxide from human aortic endothelial cells. J Nutr 2003;133:4083–
9.
82 Yu Y, Correll PH, Vanden Heuvel JP. Conjugated linoleic acid decreases production of
pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent
mechanism. Biochim Biophys Acta. 2002 15;1581(3):89-99.
83 Cheng WL, Lii CK, Chen HW, Lin TH, Liu KL. Contribution of conjugated linoleic acid to
the suppression of inflammatory responses through the regulation of the NF-kappaB
pathway. J Agric Food Chem. 2004 14;52(1):71-8.
84 DeLany JP, Blohm F, Truett AA, Scimeca JA, West D.B. Conjugated linoleic acid rapidly
reduces body fat content in mice without affecting energy intake, Am J. Physiol
1999;276:R1172–R1179.
85 Belury MA. Dietary conjugated linoleic acid in health: physiological effects and
mechanisms of action. Annu Rev Nutr 2002;22:505–531.
86 Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O.
Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy
overweight humans. Am J Clin Nutr. 2004;79(6):1118-25.
87 Eyjolfson V, Spriet LL, Dyck DJ. Conjugated linoleic acid improves insulin sensitivity in
young, sedentary humans. Med Sci Sports Exerc. 2004;36(5):814-20.
88 Steck SE, Chalecki AM, Miller P, et al. Conjugated Linoleic Acid Supplementation for
Twelve Weeks Increases Lean Body Mass in Obese Humans. J. Nutr. 2007 137 (5).
89 Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O.
Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr
2000;130:2943-2948.
www.metabolicdiet.com Page 19 of 21
90 Riserus U, Berglund L, Vessby B. Conjugated linoleic acid (CLA) reduced abdominal
adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a
randomised controlled trial. Int J Obes Relat Metab Disord. 2001;25(8):1129-35.
91 Gaullier JM, Halse J, Høye K, et al. Conjugated linoleic acid supplementation for 1 y
reduces body fat mass in healthy overweight humans. Am J Clin Nutr 2004;79:1118–
1125.
92 Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O.
Supplementation with conjugated linoleic acid for 24 months is well tolerated by and
reduces body fat mass in healthy, overweight humans. J Nutr. 2005;135(4):778-84.
93 Park Y, Albright KJ, Storkson JM, et al. Changes in body composition in mice during
feeding and withdrawal of conjugated linoleic acid, Lipids 1999;34(3):243-248.
94 Pariza MW, Park Y, Cook ME. The biologically active isomers of conjugated linoleic
acid, Prog Lipid Res 2001;40(4):283-298.
95 Choi Y, Kim YC, Han YB, et al. The trans-10,cis-12 isomer of conjugated linoleic acid
downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes, J Nutr
2000;130 (8):1920-1924.
96 Park Y, Albright KJ, Storkson JM, et al. Changes in body composition in mice during
feeding and withdrawal of conjugated linoleic acid, Lipids 1999;34(3):243-248.
97 Pariza MW, Park Y, Cook ME. The biologically active isomers of conjugated linoleic
acid, Prog Lipid Res 2001;40(4):283-298.
98 Choi Y, Kim YC, Han YB, et al. The trans-10,cis-12 isomer of conjugated linoleic acid
downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes, J Nutr
2000;130 (8):1920-1924.
99 Cook ME, Miller CC, Park Y, Pariza M. Immune modulation by altered nutrient
metabolism: nutritional control of immune-induced growth depression. Poultry Science
1993;72(7):1301-5.
100 Miller CC, Park Y, Pariza MW, Cook ME. Feeding conjugated linoleic acid to animals
partially overcomes catabolic responses due to endotoxin injection. Biochem Biophysic
Res Comm 1994;198(3):1107-12.
101 Gaullier JM, Halse J, Hoivik HO, Hoye K, Syvertsen C, Nurminiemi M, Hassfeld C,
Einerhand A, O'Shea M, Gudmundsen O. Six months supplementation with conjugated
linoleic acid induces regional-specific fat mass decreases in overweight and obese. Br J
Nutr. 2007;97(3):550-60.
102 Close RN, Schoeller DA, Watras AC, Nora EH. Conjugated linoleic acid
supplementation alters the 6-mo change in fat oxidation during sleep. Am J Clin Nutr.
2007 Sep;86(3):797-804.
103 Palacios A, Piergiacomi V, Catala A. Antioxidant effect of conjugated linoleic acid and
vitamin A during non enzymatic lipid peroxidation of rat liver microsomes and
mitochondria. Mol Cell Biochem. 2003; 250(1-2):107-13.
104 Roberts WG, Gordon MH, Walker AF. Effects of enhanced consumption of fruit and
vegetables on plasma antioxidant status and oxidative resistance of LDL in smokers
supplemented with fish oil. Eur J Clin Nutr. 2003; 57(10):1303-10.
105 Foulon T, Richard MJ, Payen N, Bourrain JL, Beani JC, Laporte F, Hadjian A. Effects of
fish oil fatty acids on plasma lipids and lipoproteins and oxidant-antioxidant imbalance in
healthy subjects. Scand J Clin Lab Invest. 1999; 59(4):239-48.
106 Rakel DP, Rindfleisch A. Inflammation: nutritional, botanical, and mind-body influences.
South Med J. 2005 Mar;98(3):303-10.
www.metabolicdiet.com Page 20 of 21
107 Ringseis R, Eder K. Insufficient dietary vitamin e increases the concentration of 7beta-
hydroxycholesterol in tissues of rats fed salmon oil. J Nutr 2002;132(12):3732-5.
108 Turini ME, Crozier GL, Donnet-Hughes A, Richelle MA. Short-term fish oil
supplementation improved innate immunity, but increased ex vivo oxidation of LDL in
man--a pilot study. Eur J Nutr. 2001 Apr;40(2):56-65.
109 Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH. Addition of
eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum
arachidonic acid accumulation in humans. J Nutr 2000; 130(8):1925-31.
110 Cook HW, Thomas SE, XU Z. Essential fatty acids and serine as plasmalogen
precursors in relation to competing metabolic pathways. Biochem Cell Biol 1991;
69(7):475-84.
111 J.K. Blusztajn JK, Richardson UI, Liscovitch M, Mauron C, Wurtman RJ. Phospholipids
in cellular survival and growth. In: I. Hanin and G.B. Ansel, Editors, Lecithin:
technological, biological, and therapeutic aspects, Plenum Press, New York 1987.
112 McDaniel MA, Maier SF, Einstein GO. Brain-specific" nutrients: a memory cure?
Nutrition. 2003 Nov-Dec;19(11-12):957-75.
113 McCarty M.F., "Policosanol safely down-regulates HMG-CoA reductase – potential as a
component of the Esselstyn regimen", Med. Hypotheses, Volume: 59, (2002), pp. 268-
279.
114 Canetti M, Moreira M, Mas R, Illnait J, Fernandez L, Fernandez J, Diaz E, Castano G. A
two-year study on the efficacy and tolerability of policosanol in patients with type II
hyperlipoproteinaemia. Int J Clin Pharmacol Res 1995, 15 (4):159-65.
115 Menendez R, Fernandez SI, Del Rio A, Gonzalez RM, Fraga V, Amor AM, Mas RM.
Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein
processing in cultured human fibroblasts. Biol Res 1994, 27 (3-4): 199-203.
116 Torres O, Agramonte AJ, Illnait J, Mas Ferreiro R, Fernandez L, Fernandez JC.
Treatment of hypercholesterolemia in NIDDM with policosanol. Diabetes Care 1995 Mar,
18 (3): 393-7.
117 Taylor JC, Rapport L, Lockwood GB. Octacosanol in human health. Nutrition 2003, 19,
192-195.
118 Stuusser R, Batista J, Pardon R, Sosa F, Pereztol O. Longterm therapy with
octacosanol improves treadmill exercise-ECG testing performance of coronary heart
disease patients. Int. J. Clin. Pharmacol. Ther. 1998, 36, 469-473.
119 Kabir Y, Kimura S. Tissue distribution of (8-14C)-octacosanol in liver and muscle of rats
after serial administration. Ann. Nutr. Metab. 1995, 39, 279-284.
120 Saint-John M, McNaughton L. Octacosanol ingestion and its effects on metabolic
responses to submaximal cycle ergometry, reaction time and chest and grip strength. Int
Clin Nutr Rev 1986;6:81
121 Cockerill DL, Bucci LR. Increases in muscle girth and decreases in body fat associated
with a nutritional supplement program. Chiropract Sports Med 1987;1:73
122 Bast A, Haenen GR. Lipoic acid: a multifunctional antioxidant. Biofactors. 2003;17(1-
4):207-13.
123 Packer L, Witt EH, Tritschler HJ. Alpha–lipoic acid as a biological antioxidant. Free
Radic Biol Med. 1995;19:227–250.
124 Jones W, Li X, Qu ZC, et al. Uptake, recycling, and antioxidant actions of alpha-lipoic
acid in endothelial cells. Free Radic Biol Med 2002;33:83-93.
www.metabolicdiet.com Page 21 of 21
125 Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-
lipoic acid. Free Radic Biol Med 1997;22(1-2):359-78.
126 Podda M, Tritschler HJ, Ulrich H, et al. Alpha–lipoic acid supplementation prevents
symptoms of vitamin E deficiency. Biochem Biophys Res Commun. 1994;204:98–104.
127 Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic
acid in the treatment of mercury toxicity. Altern Med Rev. 2002;7(6):456-71.
128 Packer L. Alpha lipoic acid: a metabolic antioxidant which regulates NF- kappaB signal
transduction and protects against oxidative injury. Drug Metab Rev 1998;30:245–75.
129 Lee HA, Hughes DA. Alpha-lipoic acid modulates NF-kappaB activity in human
monocytic cells by direct interaction with DNA. Exp Gerontol. 2002;37(2-3):401-10.
130 Maroon JC, Bost JW. Omega-3 fatty acids (fish oil) as an anti-inflammatory: an
alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol.
2006;65(4):326-31.
131 Faust A, Burkart V, Ulrich H, Weischer CH, Kolb H. Effect of lipoic acid on
cyclophosphamide-induced diabetes and insulitis in non-obese diabetic mice. Int J
Immunopharmacol. 1994;16(1):61-6.
132 Burkart V, Koike T, Brenner HH, Imai Y, Kolb H. Dihydrolipoic acid protects pancreatic
islet cells from inflammatory attack. Agents Actions. 1993;38(1-2):60-5.
133 Lateef H, Aslam MN, Stevens MJ, Varani J. Pretreatment of diabetic rats with lipoic acid
improves healing of subsequently-induced abrasion wounds. Arch Dermatol Res
2005;297(2):75-83.
134 Thirunavukkarasu V, Nandhini AT, Anuradha CV. Fructose diet-induced skin collagen
abnormalities are prevented by lipoic acid. Exp Diabesity Res. 2004;5(4):237-44.
135 Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-alpha-lipoic acid on
mitochondrial enzymes in aged rats. Chem Biol Interact. 2001 Nov 28;138(2):189-98.
136 Palaniappan AR, Dai A. Mitochondrial ageing and the beneficial role of alpha-lipoic
acid. Neurochem Res. 2007 Sep;32(9):1552-8.
